Drug tolerance & interaction

Drug tolerance & interaction

Content

• Drug interactions

• Drug food interactions

• Drug tolerance and dependence

Intended Learning Outcomes

At the end of this lecture, student will be able to  

• Describe drug interactions

• Give examples for drug interactions inside/outside the body

• Explain drug tolerance and dependence

Drug Tolerance

Mechanism of Development of Tolerance

• Pharmacokinetic (Disposition)

– Decreased intensity & contact between drug and target tissue

– Barbiturates on repeated adm – enzyme induction

– Tumor P –gp: pump out anticancer drug

• Pharmacodynamic (Functional)

– Target tissue sensitivity/ R downregulation

– Morphine/ alcohol/ barbiturate

• Tachyphylaxis

Drug Dependence

• Psychic (sometimes physical) state

• Include compulsion to take a drug on continuous/ periodic basis

• To experience psychic effects

• In absence – withdrawl symptoms

• 3 types:

– Psychic: Feeling of satisfaction

– Physical: Achieves adaptive state

– Combined 

Examples of Dependence

• Psychic + Physical

– Morphine, heroin, alcohol, barbiturate, nicotine

• Psychic + mild physical

– Nalorphine, levallorphan, amphetamine

• Only psychic

– Cocaine, LSD, psilocybin

Drug interactions

• Result from use of 2 or more drugs

• Enhanced/ diminished effect

• Useful – Synergistic combination

• Harmful – Numerous

• Inside the body

• Outside the body

Drug interactions - Outside the body

Use of wrong vehicles for infusion

• No drug to blood plasma, AA, fat emulsion, NAHCO3, mannitol

• Highly acidic solutions (dextrose, fructose): Unsuitable for Na/ K salts of weakly acidic drugs

• Isotonic saline: suitable for more drugs

Drug interactions - Inside the body - Pharmacokinetic

Absorption

• Form complexes in gut

– Sucralfate reduces BA of phenytoin

• Altering gastric pH (alters solublity)

– NaHCO3 affects Tetracycline

• Modifying gut motility and gastric emptying

– Antimuscarinic, opioids

Distribution

• Strongly bound – remain inactive

• Displacement reactions

• Increases pharmacologically active form

• Clofibrate displaces warfarin

• Salicylate displaces tolbutamide

Drug Transport

• Guanithedine transported by NA Transport System

• Inhibition by Imipramine: Interfere with antihypertensive action of Guanithedine

Drug metabolism

• Enzyme inducers and inhibitors

Drug excretion

• Facilitated / interfered

Interactions at Receptor Site

• Acting on same receptor site/ different

• Tubocurarine & AG – increased NM blockade

• Morphine + barbiturates – Increased CNS depression

Changes in electrolyte and fluid balance

• Drugs decreasing potassium may potentiate the effect of digitalis

Summary

• Drug tolerance: Pharmacokinetic (Disposition) & Pharmacodynamic (Functional)

• Drug interactions are possible inside/outside the body

• Drug dependence 3 types:

– Psychic: Feeling of satisfaction

– Physical: Achieves adaptive state

– Combined 

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